Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions.

BACKGROUND: The prevalence of patients with chronic kidney disease (CKD) and polypharmacy is increasing and has amplified the importance of examining inappropriate prescribing (IP) in CKD. This review focuses on the latest research regarding the prevalence of IP in CKD and the related adverse clinical effects and explores new interventions against IP. METHOD: A literature search was performed using PubMed, EMBASE and the Cochrane Library searching articles published between June 2016 and March 2022. RESULTS: Twenty-seven studies were included. An IP prevalence of 12.6% to 96% and 0.3% to 66% was reported in hospital and outpatient settings, respectively. In nonhospital settings, the prevalence of IP varied between 3.9% and 60%. IP was associated with higher risk of hospitalisation (HR 1.46, 95% CI 1.17-1.81), higher bleeding rate (HR 2.34, 95% CI 1.32 to 3.37) and higher risk of all-cause mortality (OR 1.07, 95% CI 1.02 to 1.13). Three studies reported the impact of interventions on IP. CONCLUSION: This review highlights widespread IP in CKD patients across healthcare settings, with varying prevalence rates. IP is substantially linked to adverse outcomes in patients. While limited interventions show promise, urgent research is needed to develop effective strategies addressing IP and improving CKD patient care.

Mannan-binding lectin serine protease-2 (MASP-2) in human kidney and its relevance for proteolytic activation of the epithelial sodium channel.

Proteolytic activation of the renal epithelial sodium channel (ENaC) is increased by aldosterone. The aldosterone-sensitive protease remains unidentified. In humans, elevated circulating aldosterone is associated with increased urinary extracellular vesicle (uEVs) excretion of mannan-binding lectin associated serine protease-2 (MASP-2). We hypothesized that MASP-2 is a physiologically relevant ENaC-activating protease. It was confirmed that MASP2 mRNA is abundantly present in liver but not in human and mouse kidneys. Aldosterone-stimulation of murine cortical colleting duct (mCCD) cells did not induce MASP-2 mRNA. In human kidney collecting duct, MASP-2 protein was detected in AQP2-negative/ATP6VB1-positive intercalated cells suggestive of MASP2 protein uptake. Plasma concentration of full-length MASP-2 and the short splice variant MAp19 were not changed in a cross-over intervention study in healthy humans with low (70 mmol/day) versus high (250 mmol/day) Na+ intake despite changes in aldosterone. The ratio of MAp19/MASP-2 in plasma was significantly increased with a high Na+ diet and the ratio correlated with changes in aldosterone and fractional Na+ excretion. MASP-2 was not detected in crude urine or in uEVs. MASP2 activated an amiloride-sensitive current when co-expressed with ENaC in Xenopus oocytes, but not when added to the bath solution. In monolayers of collecting duct M1 cells, MASP2 expression did not increase amiloride-sensitive current and in HEK293 cells, MASP-2 did not affect γENaC cleavage. MASP-2 is neither expressed nor co-localized and co-regulated with ENaC in the human kidney or in urine after low Na+ intake. MASP-2 does not mediate physiological ENaC cleavage in low salt/high aldosterone settings.